A critical challenge facing Biomedical Computing is the development of new modeling methods that incorporate realistic cellular machinery and span the wide temporal and spatial scales of cellular function. Given ever-increasing genomic and metabolic data, new programs and multidisciplinary approaches are desperately needed to "forecast cellular weather", e.g., predict complex distributions of responses to signals and stimuli. Biomedical Computing, however, extends between many scientific cultures that have had limited incentive or opportunity for ongoing collaboration. Merging efforts across these cultures to foster multiscale, integrative computational approaches is difficult, and requires concerted planning and new infrastructure. Such bridging of cultures, especially between experimental and computational research, will be a major goal of the "Pre-National Program of Excellence in Biomedical Computing" (Pre-NPEBC) efforts proposed here. Within the University of Pittsburgh and its School of Medicine, the Pittsburgh Supercomputing Center, Carnegie Mellon University, and Duquesne University, there is outstanding expertise in each discipline that contributes to Biomedical Computing, and full support for pre-NPEBC efforts embodied within a Pittsburgh Center for Biomedical Computation. The Center's focus will be Multiscale Dynamics of Cell Signaling and Regulation, and the Computational Aims will be: (1) Development of new models and simulation environments, including (i) Structural dynamics of macromolecular complexes and assemblies; (ii) Stochastic spatio-temporal dynamics of cellular microphysiology, and (iii) Nonlinear dynamics of signaling networks; (2) Integration of (i-iii) to bridge the gap between molecular and cellular models, and (3) Development of new storage, visualization, and dissemination tools for results and algorithms developed at multiple scales. The new approaches will be applied to specific biomedical problems through new collaborations between computational and experimental investigators. Initial anticipated Developmental Projects include the dynamics of: 1) nitric oxide and apoptosis; 2) DNA damage and cellular responses; and 3) signaling ligands and cascades. Educational Activities will include the planning, organization and/or establishment of new cross-disciplinary coursework, workshops, symposia, retreats, graduate and post-doctoral fellowships, certificate programs, and a cross-institutional Graduate Degree Program in Computational Biology & Bioinformatics.